Minoxidil is an arterial dilator which has been used, in oral form, in the treatment of hypertension to lower blood pressure. More recently, the drug has been shown to stimulate new hair growth, when applied topically, in cases of male pattern baldness. Initial clinical studies with a topical form of the drug indicate that reversal of male pattern baldness is most favorable in younger men, and where recent hair loss has occurred, but that new hair growth is observed in a significant percentage of older men and/or where in cases of long-term baldness.
The drug itself is a piperidinyl pirimidine compound which is poorly soluble in water and in most water-immiscible organic solvents such as chloroform. Heretofore, minoxidil has been formulated, for topical use, in an ethanol-based ointment vehicle containing ethanol, propylene glycol and water. The solubility of the drug in pure propylene glycol is between about 7-9% by weight, and in an ethanol/propylene glycol/water vehicle, only about 2%. One drawback of the formulation is the tendency of the minoxidil to revert to an insoluble crystalline form when applied to the skin, as the ethanol solvent evaporates. Whether due to the tendency of the drug to crystallize or other factors, the minoxidil formulation shows relatively inefficient uptake by the skin. Another limitation is the limited solubility of the drug in the ethanol/propylene glycol/water vehicle. Further, evaporation of ethanol, when the formulation is applied to the skin, leaves a viscous propylene glycol/water residue which may be objectionable to many users. The drug is poorly soluble in water and practically insoluble in lipophilic solvents, such as chloroform. Therefore, predominantly water-based or propellant-solvent formulations have not been feasible heretofore and it would be advantageous to have an alternative formulation avoiding the above problems.
European patent application No. 177,223 discloses a liposomal minoxidil composition in which minoxidil is present (1) in solution form possibly in a supersaturated state, either encapsulated in lipid vesicles, or in the aqueous or lipid phases of a liposome suspension, and (2) in a finely divided crystalline (solid) form both within and outside the lipid vesicles. Preferred embodiments of the composition are formed by hydrating a minoxidil lipid film containing a saturated phosphatidylcholine (PC), such as dipalmitoylphosphatidylcholine (DPPC), cholesterol, and minoxidil in ethanol/propylene glycol and water. Minoxidil is present at a final weight concentration of between about 1.2-3%. The composition was found to contain liposomes of various sizes between about 1 .mu. to 15 .mu., and more importantly minoxidil crystals. Although the formulation is reported to increase drug uptake by the epidermis when applied topically to skin, it has the same limitation as the above non-liposomal formulation in that the drug is applied to the skin largely in crystalline form.